This project is concerned with investigating the in vivo differentiation of the thymus-dependent lymphocyte and its interaction in vitro with foreign cells by means of correlated techniques of conventional electron microscopy, freeze-fracturing, and ultrastructural cytochemistry. A pure population of sensitized thymus-dependent lymphocytes, obtained by culturing cortisone-resistant thymocytes with mitomycin-treated allogeneic spleen cells will be mixed with target cells in vitro and their interaction studied using the freeze-fracturing technique. The membrane events leading to target cell lysis will also be analyzed and compared to those produced by antibody and complement. The development of the blood-thymus barrier will be studied in the newborn mouse.